Temporal pattern classification of PM2.5 chemical compositions in Seoul, Korea using K-means clustering analysis.

Particulate matter with a diameter ≤ 2.5 µm (PM2.5) is a complex mixture of particles with a variety of compositions potentially including sulfate ions (SO42-), nitrate ions (NO3-), ammonium ions (NH4+), organic and inorganic elemental carbon, and metals. Here, the temporal composition evolution of PM2.5 was analyzed to characterize its emission source, origin, and external influences. The concentrations of wintertime PM2.5 chemical compositions in Seoul, Korea during the period of 2012-2021 were classified into four representative clusters using a K-means cluster analysis method. Cluster 1 exhibited high concentrations of NO3- and NH4+ ions mainly due to the prevalence of emissions from domestic manure and fertilizer sources in the northeast. High concentrations of these two ions are conducive to generation of ammonium nitrate (NH4NO3) through atmospheric chemical reactions, resulting in relatively long-lasting high PM2.5 concentrations in Seoul. In cluster 2, high concentrations of SO42-, vanadium, and nickel were observed in frequent south-westerly winds, indicating the domestic influence of industrial facilities. Cluster 3 showed high concentrations of potassium ions and organic carbon, highlighting a pronounced external influence transported from China via prevailing westerly winds. Cluster 4 showed low PM2.5 concentrations accompanied by strong winds in warm environments, which are uncommon in winter. This study revealed that the air quality in Seoul, which was influenced by many factors, could be classified into four representative patterns. Our results provide insights into the emission sources, major influences, and responsible mechanisms of high PM2.5 concentrations in Seoul, which can help with air quality policies.

The relationship of age and comorbid conditions to hospital and nursing home days in Medicaid recipients with HIV.

OBJECTIVE: To determine how aging impacts healthcare utilization in persons with HIV (PWH) compared with persons without HIV (PWoH). DESIGN: Matched case-control study. METHODS: We studied Medicaid recipients in the United States, aged 18-64 years, from 2001 to 2012. We matched each of 270 074 PWH to three PWoH by baseline year, age, gender, and zip code. Outcomes were hospital and nursing home days per month (DPM). Comorbid condition groups were cardiovascular disease, diabetes, liver disease, mental health conditions, pulmonary disease, and renal disease. We used linear regression to examine the joint relationships of age and comorbid conditions on the two outcomes, stratified by sex at birth. RESULTS: We found small excesses in hospital DPM for PWH compared with PWoH. There were 0.03 and 0.07 extra hospital DPM for female and male individuals, respectively, and no increases with age. In contrast, excess nursing home DPM for PWH compared with PWoH rose linearly with age, peaking at 0.35 extra days for female individuals and 0.4 extra days for male individuals. HIV-associated excess nursing home DPM were greatest for persons with cardiovascular disease, diabetes, mental health conditions, and renal disease. For PWH at age 55 years, this represents an 81% increase in the nursing home DPM for male individuals, and a 110% increase for female individuals, compared PWoH. CONCLUSION: Efforts to understand and interrupt this pronounced excess pattern of nursing home DPM among PWH compared with PWoH are needed and may new insights into how HIV and comorbid conditions jointly impact aging with HIV.

Millennial-scale variability of Greenland dust provenance during the last glacial maximum as determined by single particle analysis.

Greenland ice core records exhibited 100-fold higher dust concentrations during the Last Glacial Maximum (LGM) than during the Holocene, and dust input temporal variability corresponded to different climate states in the LGM. While East Asian deserts, the Sahara, and European loess have been suggested as the potential source areas (PSAs) for Greenland LGM dust, millennial-scale variability in their relative contributions within the LGM remains poorly constrained. Here, we present the morphological, mineralogical, and geochemical characteristics of insoluble microparticles to constrain the provenance of dust in Greenland NEEM ice core samples covering cold Greenland Stadials (GS)-2.1a to GS-3 (~ 14.7 to 27.1 kyr ago) in the LGM. The analysis was conducted on individual particles in microdroplet samples by scanning electron microscopy with energy dispersive X-ray spectroscopy and Raman microspectroscopy. We found that the kaolinite-to-chlorite (K/C) ratios and chemical index of alteration (CIA) values were substantially higher (K/C: 1.4 ± 0.7, CIA: 74.7 ± 2.9) during GS-2.1a to 2.1c than during GS-3 (K/C: 0.5 ± 0.1, CIA: 65.8 ± 2.8). Our records revealed a significant increase in Saharan dust contributions from GS-2.1a to GS-2.1c and that the Gobi Desert and/or European loess were potential source(s) during GS-3. This conclusion is further supported by distinctly different carbon contents in particles corresponding to GS-2.1 and GS-3. These results are consistent with previous estimates of proportional dust source contributions obtained using a mixing model based on Pb and Sr isotopic compositions in NEEM LGM ice and indicate millennial-scale changes in Greenland dust provenance that are probably linked to large-scale atmospheric circulation variabilities during the LGM.

Use of Diabetes Medications before and after a Heart Failure-Related Hospitalization among Nursing Home Residents.

OBJECTIVES: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardiovascular benefits, whereas thiazolidinediones (TZDs) and sulfonylureas (SUs) increase cardiovascular risk. The objective of this study was to describe the use of SGLT-2is, GLP-1RAs, TZDs, and SUs before and after a heart failure (HF)-related hospitalization in nursing home (NH) residents with type 2 diabetes (T2D). DESIGN: This was a cohort study using a 20% sample of Medicare claims linked with Minimum Data Set resident assessments. SETTING AND PARTICIPANTS: The study population was long-stay NH residents with T2D and an HF-related hospitalization between January 1, 2013, and August 31, 2018. For individuals with multiple HF hospitalizations, 1 hospitalization was randomly selected. METHODS: We ascertained diabetes medications using Medicare Part D claims during the 120 days before and after hospital discharge (or skilled nursing facility discharge, where applicable). We calculated (1) the proportion of study participants who received a medication class of interest during pre- and posthospitalization periods; (2) the proportion of continuous users; and (3) the proportion of posthospitalization users who were new users. RESULTS: A total of 12,990 NH residents with T2D and an HF-related hospitalization were included (mean age 78 years, 66% female, 19% Black). Before hospitalization, 1.5% received TZDs, 14.1% received SUs, 1.2% received GLP-1RAs, and 0.3% received SGLT-2is. Among prehospitalization users of TZDs, SUs, GLP-1RAs, and SGLT-2is, 49%, 62%, 60%, and 40% continued the medications, respectively. Among posthospitalization users of TZDs, SUs, GLP-1RAs, and SGLT-2is, 37%, 10%, 28%, and 11%, respectively, were new users. CONCLUSIONS: Among NH residents with hospitalized HF, GLP-1RAs and SGLT-2is were seldom used. TZDs and SUs were still used by many residents with T2D after HF hospitalizations. IMPLEMENTATIONS: Barriers may exist in the use of newer diabetes medications to prevent heart failure in NH residents with T2D, which warrants further studies in older adults with multimorbidity.

Comparative Persistence of Non-tumor Necrosis Factor (TNF) vs. TNF Antagonists for Post-operative Prophylaxis in Crohn's Disease (CD).

BACKGROUND: The comparative safety and effectiveness of available biologics for post-operative prophylaxis in Crohn's disease (CD) is uncertain. Drug persistence may serve as a real-world proxy for tolerability and effectiveness. We evaluated the comparative persistence of non-TNF and TNF antagonists for post-operative prophylaxis and their comparative effectiveness for preventing early endoscopic post-operative recurrence (POR). METHODS: We conducted a single-center, retrospective study of surgically naïve CD subjects undergoing ileocecal or small bowel resection between 1/1/2000 and 12/31/2021 and prescribed a biologic for post-operative prophylaxis. We compared the risk of prophylaxis failure (requiring recurrent surgery or discontinuation of therapy due to persistent POR despite optimized drug level or dose escalation, immunogenicity, and/or adverse event) and early endoscopic POR (Rutgeert's score ≥ i2 within 15 months postoperatively) between non-TNF and TNF antagonist prophylaxis using Cox proportional hazard and logistic regression, respectively, adjusting for demographic and disease characteristics. RESULTS: The study included 291 subjects (81% TNF antagonists). After multivariable adjustment, non-TNF antagonist prophylaxis was associated with a significantly lower risk of prophylaxis failure than TNF antagonists (hazard ratio 0.26; 95% confidence interval (CI) [0.13-0.53]). Prophylaxis with non-TNF and TNF antagonists had similar risk of early endoscopic POR (odds ratio 0.66; 95% CI [0.32-1.36]). Stratifying the non-TNF antagonists by anti-integrin and anti-IL12/23 yielded similar results. CONCLUSION: In a cohort of surgically naïve CD subjects prescribed a biologic for post-operative prophylaxis, non-TNF antagonists had greater persistence than TNF antagonists with similar risk for early endoscopic POR. If confirmed by large, prospective studies, these findings can inform post-operative management strategies in CD.

Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

BACKGROUND: Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). METHODS: This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. RESULTS: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. CONCLUSIONS: Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Inhalable Nitric Oxide Delivery Systems for Pulmonary Arterial Hypertension Treatment.

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated blood pressure in the pulmonary arteries. Nitric oxide (NO) is a gaseous signaling molecule with potent vasodilator effects; however, inhaled NO is limited in clinical practice because of the need for tracheal intubation and the toxicity of high NO concentrations. In this study, inhalable NO-releasing microspheres (NO inhalers) are fabricated to deliver nanomolar NO through a nebulizer. Two NO inhalers with distinct porous structures are prepared depending on the molecular weights of NO donors. It is confirmed that pore formation can be controlled by regulating the migration of water molecules from the external aqueous phase to the internal aqueous phase. Notably, open porous NO inhalers (OPNIs) can deliver NO deep into the lungs through a nebulizer. Furthermore, OPNIs exhibit vasodilatory and anti-inflammatory effects via sustained NO release. In conclusion, the findings suggest that OPNIs with highly porous structures have the potential to serve as tools for PAH treatment.

Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus.

Normal pressure hydrocephalus (NPH) patients had altered white matter tract integrities on diffusion tensor imaging (DTI). Previous studies suggested disproportionately enlarged subarachnoid space hydrocephalus (DESH) as a prognostic sign of NPH. We examined DTI indices in NPH subgroups by DESH severity and clinical symptoms. This retrospective case-control study included 33 NPH patients and 33 age-, sex-, and education-matched controls. The NPH grading scales (0-12) were used to rate neurological symptoms. Patients with NPH were categorized into two subgroups, high-DESH and low-DESH groups, by the average value of the DESH scale. DTI indices, including fractional anisotropy, were compared across 14 regions of interest (ROIs). The high-DESH group had increased axial diffusivity in the lateral side of corona radiata (1.43 ± 0.25 vs. 1.72 ± 0.25, p = 0.04), and showed decreased fractional anisotropy and increased mean, and radial diffusivity in the anterior and lateral sides of corona radiata and the periventricular white matter surrounding the anterior horn of lateral ventricle. In patients with a high NPH grading scale, fractional anisotropy in the white matter surrounding the anterior horn of the lateral ventricle was significantly reduced (0.36 ± 0.08 vs. 0.26 ± 0.06, p = 0.03). These data show that DESH may be a biomarker for DTI-detected microstructural alterations and clinical symptom severity.

Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

ADSC secretome constrains NK cell activity by attenuating IL-2-mediated JAK-STAT and AKT signaling pathway via upregulation of CIS and DUSP4.

BACKGROUND: Mesenchymal stem cells (MSCs) have immunomodulatory properties and therapeutic effects on autoimmune diseases through their secreted factors, referred to as the secretome. However, the specific key factors of the MSC secretome and their mechanisms of action in immune cells have not been fully determined. Most in vitro experiments are being performed using immune cells, but experiments using natural killer (NK) cells have been neglected, and a few studies using NK cells have shown discrepancies in results. NK cells are crucial elements of the immune system, and adjustment of their activity is essential for controlling various pathological conditions. The aim of this study was to elucidate the role of the adipose tissue-derived stem cell (ADSC) secretome on NK cell activity. METHODS: To obtain the ADSC secretome, we cultured ADSCs in medium and concentrated the culture medium using tangential flow filtration (TFF) capsules. We assessed NK cell viability and proliferation using CCK-8 and CFSE assays, respectively. We analyzed the effects of the ADSC secretome on NK cell activity and pathway-related proteins using a combination of flow cytometry, ELISA, cytotoxicity assay, CD107a assay, western blotting, and quantitative real-time PCR. To identify the composition of the ADSC secretome, we performed LC-MS/MS profiling and bioinformatics analysis. To elucidate the molecular mechanisms involved, we used mRNA sequencing to profile the transcriptional expression of human blood NK cells. RESULTS: The ADSC secretome was found to restrict IL-2-mediated effector function of NK cells while maintaining proliferative potency. This effect was achieved through the upregulation of the inhibitory receptor CD96, as well as downregulation of activating receptors and IL-2 receptor subunits IL-2Rα and IL-2Rγ. These changes were associated with attenuated JAK-STAT and AKT pathways in NK cells, which were achieved through the upregulation of cytokine-inducible SH2-containing protein (CIS, encoded by Cish) and dual specificity protein phosphatase 4 (DUSP4). Furthermore, proteomic analysis revealed twelve novel candidates associated with the immunomodulatory effects of MSCs. CONCLUSIONS: Our findings reveal a detailed cellular outcome and regulatory mechanism of NK cell activity by the ADSC secretome and suggest a therapeutic tool for treating NK-mediated inflammatory and autoimmune diseases using the MSC secretome.

Identifying Mitral Valve Prolapse at Risk for Arrhythmias and Fibrosis From Electrocardiograms Using Deep Learning.

BACKGROUND: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) is a marker of arrhythmic risk associated with myocardial fibrosis and increased mortality in MVP. OBJECTIVES: The authors sought to evaluate whether electrocardiogram (ECG)-based machine learning can identify MVP at risk for ComVE, death and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging. METHODS: A deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients from the University of California-San Francisco between 2012 and 2020. A separate CNN was trained to detect late gadolinium enhancement (LGE) using 1,369 ECGs from 87 MVP patients with contrast CMR. RESULTS: The prevalence of ComVE was 28% (160/569). The area under the receiver operating characteristic curve (AUC) of the CNN to detect ComVE was 0.80 (95% CI: 0.77-0.83) and remained high after excluding patients with moderate-severe mitral regurgitation [0.80 (95% CI: 0.77-0.83)] or bileaflet MVP [0.81 (95% CI: 0.76-0.85)]. AUC to detect all-cause mortality was 0.82 (95% CI: 0.77-0.87). ECG segments relevant to ComVE prediction were related to ventricular depolarization/repolarization (early-mid ST-segment and QRS from V1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 24% patients with available CMR; AUC for detection of LGE was 0.75 (95% CI: 0.68-0.82). CONCLUSIONS: CNN-analyzed 12-lead ECGs can detect MVP at risk for ventricular arrhythmias, death and/or fibrosis and can identify novel ECG correlates of arrhythmic risk. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.

A Moonlighting Protein Secreted by a Nasal Microbiome Fortifies the Innate Host Defense Against Bacterial and Viral Infections.

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

Food Insecurity during the Pandemic in South Korea: The Effects of University Students' Perceived Food Insecurity on Psychological Well-Being, Self-Efficacy, and Life Satisfaction.

This study examined the impact of university students' perceptions of food insecurity on psychological well-being, self-efficacy, and life satisfaction and observed that the students' gender plays a moderating role in this causal relationship, based on a total of 491 university students who participated in this empirical study. This study used SPSS (Version 22.0) and AMOS (Version 20.0) for the analyses. This study examines the structural relationship of this causal model. Our findings suggest that students' perceived food insecurity negatively affects the status of their psychological well-being and self-efficacy. However, contrary to expectations, perceived food insecurity has no negative effects on students' life satisfaction. In addition, the level of students' psychological well-being positively influences their life satisfaction, while self-efficacy does not. The moderating effects of gender differences in this research were also disclosed. Limitations and future research directions are also discussed.

Antiretroviral Therapy Use Was Not Associated with Stillbirth or Preterm Birth in an Analysis of U.S. Medicaid Pregnancies to Persons with HIV.

Background: Using a U.S. based, nationally representative sample, this study compares stillbirth and preterm birth outcomes between women living with HIV (WWH) who did and did not use antiretroviral therapy (ART) during pregnancy, additionally assessing ART duration and regimen type. Methods: Using 2001 to 2012 Medicaid Analytic eXtract (MAX) data from the 14 states with the highest prevalence of HIV. We estimated two, propensity score matched, multivariate logistic regression models for both outcomes of stillbirth and preterm birth: (1) any ART use and (2) the number of months on ART during pregnancy for ART users, adjusting for patient-level covariates. Results: Only 34.6% of pregnancies among WWH had a history of ART use and among those, the proportions of stillbirth and preterm birth were 0.9% and 7.9%, respectively. Any ART use was not significantly associated with either outcome of stillbirth (marginal effects [MEs]: 0.06%, 95% confidence interval [CI]: -0.17 to 0.28) or preterm birth (ME: -0.12%, 95% CI: -0.79 to 0.55). For ART users, duration of ART was not significantly associated with either outcome. Black race was a strong independent predictor in both models (stillbirth: 0.80% and 0.84%, preterm birth: 4.19% and 3.76%). Neither protease inhibitor (PI) nor boosted PI regimens were more strongly associated with stillbirth or preterm birth than nucleoside reverse transcriptase inhibitor-based regimens. Conclusion: ART use during pregnancy was low during this period. Our findings suggest that ART use and ART regimen are not associated, positively or negatively, with stillbirth or preterm birth for mothers with Medicaid. Additionally, our findings highlight a persisting need to address disparities in these outcomes for Black women.

How All-Payer Claims Databases (APCDs) Can be Used to Examine Changes in Professional Spending: Experience from the Rhode Island APCD.

States are increasingly the focus of health care spending reform efforts given political deadlock at the federal level. Using the Rhode Island All-Payer Claims Database (APCD) from 2016 to 2019, a modified National Uniform Claim Committee (NUCC) provider taxonomy, and the 2021 Restructured BETOS Classification System (RBCS), we evaluate professional spending trends in commercial and Medicaid populations, identify specialties and clinical service categories driving trends, and examine price and volume contributions to spending changes. We found that professional spending from 2016-2019 in Medicaid is increasing faster than professional spending in commercial (5.2% vs. 2.7% annually). We also found that nurse practitioner and physician assistant evaluation and management (E&M), behavioral health services E&M, anesthesia, diagnostic radiology imaging, and orthopedic procedures were among the largest areas of spending increase during the study period in Rhode Island. Three-year trends showed heterogeneity in whether volume or price was primarily responsible for these spending increases.

Trends in COVID-19-Related Medication Use in US Nursing Homes, 2018-2022.

OBJECTIVES: Little is known about how COVID-19 treatment patterns have evolved over time in nursing homes (NHs) despite the devastating effects of COVID-19 in this setting. The aim was to describe changes in COVID-19-related medication use over time among NH residents in the United States. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: This study used electronic health records (EHR) from 11 different US NH corporations between January 1, 2018, and March 31, 2022. METHODS: The use of medications approved for COVID-19-related conditions or known to be used off-label for COVID-19 during the study period is identified. We described trends in the use of each drug and combined use per 1000 NH residents over calendar time [quarters (Q)]. RESULTS: A total of 59,022 unique residents with the use of an eligible medication were identified. Hydroxychloroquine use sharply increased from 9.8 in 2020Q1 to 30.2 orders per 1000 individuals in 2020Q2. Dexamethasone use increased sharply from 14.8 in 2020Q2 to a peak of 121.9 orders per 1000 individuals in 2020Q4. Azithromycin use increased from 44.1 in 2019Q3 to a peak of 99.9 orders per 1000 individuals in 2020Q4, with a drop in 2020Q3 of 51.3 per 1000 individuals in 2020Q3. Concurrent use of azithromycin and hydroxychloroquine increased sharply from 0.3 in 2020Q1 to 10.6 orders per 1000 residents in 2020Q2 and then drastically decreased to 0.6 per 1000 residents in 2020Q3. Concurrent use of dexamethasone and azithromycin rose considerably from 0.7 in 2020Q2 to 28.2 orders per 1000 residents in 2020Q4. CONCLUSIONS AND IMPLICATIONS: As in other settings, COVID-19-related medication use in NHs appears to have changed in response to the shifting evidence base and availability of medications during the pandemic. Providers should continue to diligently modify their prescribing as new evidence accrues.

Do radiomics or diffusion-tensor images provide additional information to predict brain amyloid-beta positivity?

The aim of the present study was to predict amyloid-beta positivity using a conventional T1-weighted image, radiomics, and a diffusion-tensor image obtained by magnetic resonance imaging (MRI). We included 186 patients with mild cognitive impairment (MCI) who underwent Florbetaben positron emission tomography (PET), MRI (three-dimensional T1-weighted and diffusion-tensor images), and neuropsychological tests at the Asan Medical Center. We developed a stepwise machine learning algorithm using demographics, T1 MRI features (volume, cortical thickness and radiomics), and diffusion-tensor image to distinguish amyloid-beta positivity on Florbetaben PET. We compared the performance of each algorithm based on the MRI features used. The study population included 72 patients with MCI in the amyloid-beta-negative group and 114 patients with MCI in the amyloid-beta-positive group. The machine learning algorithm using T1 volume performed better than that using only clinical information (mean area under the curve [AUC]: 0.73 vs. 0.69, p < 0.001). The machine learning algorithm using T1 volume showed better performance than that using cortical thickness (mean AUC: 0.73 vs. 0.68, p < 0.001) or texture (mean AUC: 0.73 vs. 0.71, p = 0.002). The performance of the machine learning algorithm using fractional anisotropy in addition to T1 volume was not better than that using T1 volume alone (mean AUC: 0.73 vs. 0.73, p = 0.60). Among MRI features, T1 volume was the best predictor of amyloid PET positivity. Radiomics or diffusion-tensor images did not provide additional benefits.

The Burden and Treatment of Chronic Constipation Among US Nursing Home Residents.

OBJECTIVE: To evaluate the burden of chronic constipation (CC) and the use of drugs to treat constipation (DTC) in 2 complementary data sources. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: US nursing home residents aged ≥65 years with CC. METHODS: We conducted 2 retrospective cohort studies in parallel using (1) 2016 electronic health record (EHR) data from 126 nursing homes and (2) 2014-2016 Medicare claims, each linked with the Minimum Data Set (MDS). CC was defined as (1) the MDS constipation indicator and/or (2) chronic DTC use. We described the prevalence and incidence rate of CC and the use of DTC. RESULTS: In the EHR cohort, we identified 25,739 residents (71.8%) with CC during 2016. Among residents with prevalent CC, 37% received a DTC, with an average duration of use of 19 days per resident-month during follow-up. The most frequently prescribed DTC classes included osmotic (22.6%), stimulant (20.9%), and emollient (17.9%) laxatives. In the Medicare cohort, a total of 245,578 residents (37.5%) had CC. Among residents with prevalent CC, 59% received a DTC and slightly more than half (55%) were prescribed an osmotic laxative. Duration of use was shorter (10 days per resident-month) in the Medicare (vs EHR) cohort. CONCLUSIONS AND IMPLICATIONS: The burden of CC is high among nursing home residents. The differences in the estimates between the EHR and Medicare data confirm the importance of using secondary data sources that include over-the-counter drugs and other treatments unobservable in Medicare Part D claims to assess the burden of CC and DTC use in this population.

Spatial transcriptomics: Technologies, applications and experimental considerations.

The diverse cell types of an organ have a highly structured organization to enable their efficient and correct function. To fully appreciate gene functions in a given cell type, one needs to understand how much, when and where the gene is expressed. Classic bulk RNA sequencing and popular single cell sequencing destroy cell structural organization and fail to provide spatial information. However, the spatial location of gene expression or of the cell in a complex tissue provides key clues to comprehend how the neighboring genes or cells cross talk, transduce signals and work together as a team to complete the job. The functional requirement for the spatial content has been a driving force for rapid development of the spatial transcriptomics technologies in the past few years. Here, we present an overview of current spatial technologies with a special focus on the commercially available or currently being commercialized technologies, highlight their applications by category and discuss experimental considerations for a first spatial experiment.